Partial Substitution of Glucose with Xylitol Prolongs Survival and Suppresses Cell Proliferation and Glycolysis of Mice Bearing Orthotopic Xenograft of Oral Cancer.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: MDPI Publishing Country of Publication: Switzerland NLM ID: 101521595 Publication Model: Electronic Cited Medium: Internet ISSN: 2072-6643 (Electronic) Linking ISSN: 20726643 NLM ISO Abbreviation: Nutrients Subsets: MEDLINE
    • Publication Information:
      Original Publication: Basel, Switzerland : MDPI Publishing
    • Subject Terms:
      Mouth Neoplasms* ; Xylitol*/pharmacology; Animals ; Cell Proliferation ; Glucose/metabolism ; Glycolysis ; Heterografts ; Humans ; Mice ; Sweetening Agents
    • Abstract:
      Many types of cancer have metabolic alterations with increased glycolysis. Identification of alternative sweeteners that do not fuel cancer is a novel approach to cancer control. The present study aimed to investigate the effects of xylitol on tumor growth and survival of mice bearing orthotopic xenograft of tongue cancers. The results showed that partial substitution of glucose with xylitol (glucose 0.35 g plus xylitol 2.06 g/kg body weight) non-significantly reduced tumor volume, and significantly prolonged the median survival time from 19 days in the control to 30.5 days in the xylitol group. Immunohistochemical data of the tongue tissue shows significantly lower intense-to-mild staining ratios of the proliferation marker Ki-67 in the xylitol than those of the control group ( p = 0.04). Furthermore, the xylitol substitution significantly reduced the expression of the rate-limiting glycolytic enzyme, phosphofructokinase-1 (PFK-1) ( p = 0.03), and showed a non-significant inhibition of PFK activity. In summary, partial substitution of glucose with xylitol at the equivalent dose to human household use of 10 g/day slows down tumor proliferation and prolongs survival of mice bearing an orthotopic oral cancer xenograft, possibly through glycolytic inhibition, with minimal adverse events. The insight warrants clinical studies to confirm xylitol as a candidate sweetener in food products for cancer survivors.
    • References:
      Trends Biotechnol. 2016 Aug;34(8):638-651. (PMID: 27265890)
      Nutrients. 2019 Aug 06;11(8):. (PMID: 31390800)
      CA Cancer J Clin. 2021 May;71(3):209-249. (PMID: 33538338)
      Science. 2009 May 22;324(5930):1029-33. (PMID: 19460998)
      Biotechnol Lett. 2015 May;37(5):983-90. (PMID: 25650339)
      Oral Microbiol Immunol. 2003 Aug;18(4):215-9. (PMID: 12823796)
      Head Neck Oncol. 2009 Aug 13;1:32. (PMID: 19678942)
      J Transl Med. 2014 Jul 21;12:208. (PMID: 25048361)
      Chem Biol Interact. 2020 Jun 1;324:109085. (PMID: 32275922)
      Nutr Cancer. 2017 Aug-Sep;69(6):862-872. (PMID: 28718681)
      Cancer Commun (Lond). 2020 Mar;40(2-3):81-92. (PMID: 32067418)
      Curr Opin Clin Nutr Metab Care. 2010 Jul;13(4):466-70. (PMID: 20473153)
      Foods. 2020 Nov 02;9(11):. (PMID: 33147854)
      Nutrients. 2021 Apr 15;13(4):. (PMID: 33920947)
      J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Sep 1;1061-1062:209-219. (PMID: 28750234)
      Biomolecules. 2020 Oct 09;10(10):. (PMID: 33050144)
      J Nat Sci Biol Med. 2017 Jan-Jun;8(1):16-21. (PMID: 28250669)
      Eur J Clin Nutr. 2007 Mar;61(3):349-54. (PMID: 16988647)
      Crit Rev Food Sci Nutr. 2015;55(11):1514-28. (PMID: 24915309)
      Annu Rev Cell Dev Biol. 2011;27:441-64. (PMID: 21985671)
      Clin Cancer Res. 2002 Jan;8(1):293-8. (PMID: 11801572)
      Chin J Cancer. 2011 Aug;30(8):508-25. (PMID: 21801600)
      Nutrients. 2019 Sep 02;11(9):. (PMID: 31480794)
      Am J Clin Nutr. 1997 Apr;65(4):947-50. (PMID: 9094877)
      Cancer Lett. 2009 Apr 18;276(2):125-35. (PMID: 18790562)
      Clin Cancer Res. 2011 Nov 1;17(21):6658-70. (PMID: 21903770)
      J Periodontol. 2014 Jun;85(6):e212-23. (PMID: 24592909)
      J Indian Soc Pedod Prev Dent. 2021 Apr-Jun;39(2):113-119. (PMID: 34341229)
      Int J Dent. 2016;2016:5967907. (PMID: 27840639)
      Oncogene. 2006 Aug 7;25(34):4633-46. (PMID: 16892078)
      Clin Cosmet Investig Dent. 2014 Nov 10;6:89-94. (PMID: 25422590)
      Asian Pac J Cancer Prev. 2020 Mar 01;21(3):577-582. (PMID: 32212781)
      Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2014 Apr;31(4):574-86. (PMID: 24447207)
      Cancer Biol Ther. 2020 Jun 2;21(6):541-548. (PMID: 32186431)
      Evid Based Dent. 2009;10(1):10-1. (PMID: 19322219)
      Semin Oncol Nurs. 2015 Feb;31(1):42-52. (PMID: 25636394)
      Nutrients. 2020 Nov 27;12(12):. (PMID: 33260906)
      Cancer Sci. 2012 Jul;103(7):1259-66. (PMID: 22494072)
    • Grant Information:
      MRG6080170 Thailand Science Research and Innovation (TSRI) and the Ministry of Higher Education, Science, Research, and Innovation (MHESI)
    • Contributed Indexing:
      Keywords: PFK; glucose; glycolysis; oral cancer; orthotopic xenograft model; sweetener; xylitol
    • Accession Number:
      0 (Sweetening Agents)
      IY9XDZ35W2 (Glucose)
      VCQ006KQ1E (Xylitol)
    • Publication Date:
      Date Created: 20220528 Date Completed: 20220531 Latest Revision: 20220716
    • Publication Date:
      20240104
    • Accession Number:
      PMC9148106
    • Accession Number:
      10.3390/nu14102023
    • Accession Number:
      35631164